Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1-11.23
Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1-11.23
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DOI：
10.1086/318788
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发表时间：
2001-03-01
影响因子：
9.8
通讯作者：
Curtis, D
中科院分区：
文献类型：
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作者：
Gurling, HMD;Kalsi, G;Curtis, D
我们对13个多发性精神分裂症家系进行了遗传连锁分析，以检验精神分裂症遗传亚型存在广泛的连锁异质性的假设。我们的策略包括选择13个家族，包含三代或三代以上的多个受影响的病例，没有双相情感障碍，以及一个单一的精神分裂症祖先来源，并单向传播到采样的亲属的分支。来自这些家庭的DNA样本进行了基因分型与365微卫星标记在整个基因组中以类似的10厘米的间隔。我们在5个不同的基因座上观察到LOD得分>3.0，无论是在整个样本中还是在单个家族中，强烈表明病因异质性。在1q33.2（LOD评分3.2; P = .0003）、5q33.2（LOD评分3.6; P =.0001）、8p22.1-22（LOD评分3.6; P =.0001）和11 q21（LOD评分3.1; P = .0004）处发现了样本整体异质性LOD评分>3.0。在4 q13 -31（LOD评分3.2; P = .0003）和11q23.3-24（LOD评分3.2; P = .0003）发现单个家系内LOD评分>3.0。在同一家系中，20q12.1-11.23的LOD值为2.9。事实上，其他研究也检测到1q33.2，5q33.2，8 p21 -22和11 q21的LOD得分>3.0，这表明这些区域确实存在精神分裂症易感基因座。我们相信，与染色体1 q22、5q33.2和8 p21 -22位点连锁的证据的权重现在足以证明通过基于连锁不平衡的方法对这些区域进行深入调查是合理的。这样的研究将很快允许识别对精神分裂症易感性有直接影响的突变。
We have performed genetic linkage analysis in 13 large multiply affected families, to test the hypothesis that there is extensive heterogeneity of linkage for genetic subtypes of schizophrenia. Our strategy consisted of selecting 13 kindreds containing multiple affected cases in three or more generations, an absence of bipolar affective disorder, and a single progenitor source of schizophrenia with unilineal transmission into the branch of the kindred sampled. DNA samples from these families were genotyped with 365 microsatellite markers spaced at similar to 10-cM intervals across the whole genome. We observed LOD scores >3.0 at five distinct loci, either in the sample as a whole or within single families, strongly suggesting etiological heterogeneity. Heterogeneity LOD scores >3.0 in the sample as a whole were found at 1q33.2 (LOD score 3.2; P = .0003), 5q33.2 (LOD score 3.6; P = .0001), 8p22.1-22 (LOD score 3.6; P = .0001), and 11q21 (LOD score 3.1; P = .0004). LOD scores >3.0 within single pedigrees were found at 4q13-31 (LOD score 3.2; P = .0003) and at 11q23.3-24 (LOD score 3.2; P = .0003). A LOD score of 2.9 was also found at 20q12.1-11.23 within in a single family. The fact that other studies have also detected LOD scores >3.0 at 1q33.2, 5q33.2, 8p21-22 and 11q21 suggests that these regions do indeed harbor schizophrenia-susceptibility loci. We believe that the weight of evidence for linkage to the chromosome 1q22, 5q33.2, and 8p21-22 loci is now sufficient to justify intensive investigation of these regions by methods based on linkage disequilibrium. Such studies will soon allow the identification of mutations having a direct effect on susceptibility to schizophrenia.